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The effect of resiquimod (R-848), an immune-response modifier that is similar to imiquimod, on recurrent herpes simplex virus (HSV) was evaluated using the guinea pig model of genital herpes. Guinea pigs were intravaginally infected with HSV-2 and then were randomized on day 14 to receive nothing or 0.1 mL/kg per dose of subcutaneous resiquimod, given either daily, every other day, or weekly from days 15-35. During a 3-week course of therapy, recurrences in all 3 treated groups were reduced by &gt;80%, compared with the control group. After therapy, recurrences remained significantly (P&lt;.05) decreased in all 3 groups for the next 3 weeks. The group treated weekly developed the fewest recurrences. Significant increases in interleukin-2 levels, produced by incubation of mononuclear cells with HSV-2 antigens, but not in circulating antibody also were detected in the treated groups. Resiquimod treatment may offer significant advantages to present antiviral therapies for the control of recurrent genital herpes.

Daily or Weekly Therapy with Resiquimod (R‐848) Reduces Genital Recurrences in Herpes Simplex Virus–Infected Guinea Pigs during and after Treatment